Process for preparing semisolid emulsions

ABSTRACT

A process is provided for preparing semisolid emulsions (creams) wherein a hot oil phase and a cold aqueous phase are mixed under conditions of high shear to interdisperse and homogenize the phases and with a second thereafter cause them to congeal and form a cream. Emulsifiers are included in either or both of the phases or can be separately mixed with the two phases.

United States Patent Cilento et a1.

[ 3,635,834 Jan. 18,1972

PROCESS FOR PREPARING SEMISOLID EMULSIONS Inventors: Rudolfo Cilento,North Brunswick; Robert M. Cohn, Colonia, both of NJ.

Assignee: E. R. Squibb & Sons, Inc., New York,

Filed: Dec. 22, 1969 Appl. No.: 886,810

US. Cl ..252/3l4, 252/309, 252/311, 252/31 1.5, 252/312, 424/170,424/172 Int. Cl. ..B0lj 13/00 [56] References Cited UNITED STATESPATENTS 2,254,049 8/1941 Schutte ..252/314 2,575,874 11/1951 Herlow..252/314 X Primary Examiner-Richard D. Lovering Attorney-Lawrence S.Levinson, Merle J. Smith, Theodore J. Criares, Donald J. Perrella andBurton Rodney [5 7] ABSTRACT A process is provided for preparingsemisolid emulsions (creams) wherein a hot oil phase and a cold aqueousphase are mixed under conditions of high shear to interdisperse andhomogenize the phases and with a second thereafter cause l 4; 2 0, Fieldof Search 252,309 3 l 31 4 4/17 them to congeal and form a cream.Emulslfiers are Included In eIther or both of the phases or can beseparately mixed with the two phases.

1 Claims, 1 Drawing Figure 92 24 COLD AQUEOUS PHASE SUPP TEMPERATURETEMPERATURE HOT PHASE LY TANK SUPPLY TANK (EQUIPPED WITH AGITATOR)MONITOR MONITOR (EQUIPPED wITH AGITATOR) FLOW 30 METER 34 32 l 44 HIGH46 42 SHEAR v p 26 MIXER CREAM PRODUCT 52/ TANK PROCESS FOR PREPARINGSEMISOLID EMULSIONS Creams or cream bases are prepared by a three'stepbatch operation wherein (l) a hot oil phase and hot water phase arebrought together; (2) the two phases are thoroughly mixed to cause thetwo phases to form a substantially homogeneous mixture; and then (3) thehomogeneous mixture is cooled until the mixture congeals and forms acream.

This procedure has been generally accepted throughout the pharmaceuticalindustry for preparing cream bases, notwithstanding the fact that itentails three separate operations and the restricted production time andextensive material handling attendant with these operations.

In accordance with the present invention, a process for preparing creamsor cream basesis provided which can be carried out continuously andwhich is substantially more efficient, producing substantially moreproduct and requiring substantially less material handling than priorart three-step operations.

The process of the invention for preparing semisolid emulsions (creamsor cream bases) comprises mixing a hot oil phase and a cold aqueousphase under conditions of high shear to interdisperse and homogenize thephases and cause them to congeal.

The creams or cream bases which can be prepared in accordance with theprocess of the invention are semisolid emulsions of either theoil-in-water or the water-in-oil type. The creams include from about 10to about 90 percent by weight of an oil phase, from about 90 to about 10percent by weight of an aqueous phase. The oil phase generally comprisesfrom about 70 to about 90 percent by weight of an oil material such aspetrolatum or isopropyl palmitate. Other ingredients which can bepresent in the oil phase include, for example, emulsifiers, emollients,such as sorbitol, propylene glycol and/or spermaceti or other waxes,perfumes and/or pharmaceuticals.

The aqueous phase generally includes from about 70 to about 90 percentby weight of water and from about 10 to about 30 percent by weight ofemulsifiers, emollients, such as described above and/or preservatives.Other ingredients which can be present in the aqueous phase includeantifoam agents, pharmaceuticals, perfumes and dyes.

The emulsifier will be included in either or both of the oil or aqueousphases or can be separately mixed with the two phases. Emulsifierssuitable for use herein are those of the anionic, cationic and nonionictypes as will be apparent to those skilled in the art.

Other ingredients which can be included in either or both the aqueousphase or oil phase separately or mixed with the two phases includepharmaceutically active agents, film-forming agents, astringents,deodorants, color, perfume, opacifiers, antifoam agents and/or solvents.

In carrying out the continuous process of the invention, a hot oil phaseand a cold aqueous phase are fed at controlled flow rates into a zone ofhigh shear, that is, into a high-shear mixer. The flow rates of the twophases can be varied depending upon the temperature of the phases, theshear produced in the mixer and the size of the mixer. However, the flowrates of each of the phases should be controlled so that the congealedmaterial will include the desired proportions of ingredients present ineach of the phases. Thus, the flow ratio of the oil phase to the aqueousphase can be within the range of from about 5:1 to about 1:5 andpreferably from about 1:1 to about 1:5. The temperature of the oil phaseshould be from about l to about 40 C. and preferably from about 25 toabout 35 C. above the congealing point of the two phases and the aqueousphase should be from about 20 to about C. and preferably from about toabout 10 C. below the congealing point of the two phases, in order toensure that the phases will congeal after homogenization occurs and thatthe congealed product will be substantially homogeneous in composition.Thus, for example, the oil phase can be heated to a temperature withinthe range from about 60 to about 90 C. preferably from about 75 to 85 C.and the aqueous phase can be at a temperature within the range fromabout to about 45 C., preferably from about to about C.

Under the above conditions and employing a high-shear mixer, one phasewill be finely dispersed in the other phase, that is, the two phaseswill be homogenized and thereafter will be congealed within a very shortperiod, for example, in less than a second without need for a specialcooling operation. However, if desired, the temperature of each of thephases and/or the degree of shear can be adjusted so that thetemperature of the homogeneous dispersion of the phases is substantiallyabove (for example, is l to l0 C. above) its congelation point. Thedispersion can then be cooled to effect congelation and the formation ofa cream or cream base.

The zone of high shear can be of any of the high-shear-type mixers knownin the art, such as, for example, colloid mills, homomixers orhomogenizers, ultrasonic energy mixers, paddle or arm mixers, propellermixers, including those of the helical type, turbine orcentrifugal-impeller mixers or Votators.

The degree of shear required to disperse and homogenize the two phaseswill depend upon the nature, temperature and flow rates of the phasesand is easily arrived at by trial and error as will be apparent to oneskilled in the art.

The colloid-type mill is a preferred high-shear mixer in that it impartsa high degree of shear in a very short time so that the two phases canbe interdispersed and homogenized before congealing takes place. The twophases are fed between a rapidly revolving solid rotor and its casing,which it clears by 0.001 in. or less. The rotor may or may not begrooved, ant it may or may not be conical. The two phases are subjectedto intense shear and intense centrifugal force and the combination actsto make excellent dispersions. In addition, the colloid mill has theadvantage of giving continuous flow and therefore is par1icularly suitedfor use in the continuous process of the invention.

The degree of shear produced in the colloid mill is controlled by millspeed which on conventional mills can vary between 1,000 and 10,000 rpm.and the rotor-stator (or casing) gap which can vary between 2 to 20mils. It is preferred to employ maximum speed available and about a 6mil gap.

The attached FIGURE is a schematic drawing of a preferred apparatussetup for carrying out the continuous process of the invention.

In the FIGURE, cold aqueous phase tank 10 equipped with agitator (notshown) and temperature control means 12 is positioned in communicationwith aqueous phase pump 14 via line 16, flow meter 18 and line 20. Hotoil phase tank 22 equipped with agitator (not shown) and temperaturecontrol means 24 is positioned in communication with oil phase pump 26via line 28, flow meter 30 and line 32. Pumps 14 and 26 are incommunication with high-shear mixer 34 via line 36, threeway valve 38,line 40 and via line 42, three-way valve 44, line 46, respectively.Recycle line 48 from valve 38 leads back to aqueous phase tank 10 andrecycle line 50 from valve 44 leads back to oil phase tank 22. Creamproduct tank 52 connects with a mixer 34 via line 54.

The following examples in the opinion of the inventor representspreferred embodiments of his invention:

EXAMPLE 1 Oil Phase I: by weight Glyceryl monostearate NF 50 spermacetiU.S.P. l5 Cetyl alcohol NF 7.5 lsopropyl palmilate 7.5

Tween 60 (Polyoxyethylene wrbitan stearate) 20 The aqueous phase has thefollowing composition:

Aqueous phase I: by weight Purified water U.S.P. 95.00 Propylene glycolU.S.P. 4.78 Methyl p-hydroxybcnzoate U.S.P. 0.20 Propyl phydroxybenzoate U.S.P. 0.02

Oil pump 26 is started and is adjusted to pump oil phase from the tank22 at a flow rate of about 3 kg./min. and valve 44 is set so that theoil phase is recycled via line 50 back to the hot oil phase supply tank22.

Water pump 14 is started and the flow rate of aqueous phase from tank isadjusted at about 12 kg./min. Valve 38 is set for recycling about 12kg./min. cold aqueous phase back to the aqueous phase tank 10.

The colloid mill 34 is started and the rotor speed is set at 3,000r.p.m. and the rotor-stator gap is set at 6 mils. Valves 38 and 44 arethen adjusted so that the aqueous phase and the oil phase aresimultaneously fed at 3 kg./min. and 12 kg./min., respectively, throughthe flow meters 18, 30 and pumps 14, 26, respectively, to the colloidmill. The two phases are interdispersed and homogenized in the mill andcongealed at 48-50 C. to a cream base. The congealed product gravityflows out of the mill and is continuously collected in the cream producttank 54.

EXAMPLE 2 In a manner similar to that described in example 1, thefollowing aqueous phase and oil phase are formed into a cream ase:

Aqueous phase by weight Sorbitol solution U.S.P. 8.00 Methylparahydroxy-benzoate U.S.P. 0.50 Propyl parahydroxy-benzoate U.S.P. 0.05Purified water USP. 9 l .45

Oil phase I: by weight What is claimed is:

l. A continuous process for preparing a semisolid emulsion of thewater-in-oil or oil-in-water type, which comprises passing an oil phaseat a temperature within the range of from about 60 to about C. and amaqueous phase at a temperature within the range from about 25 to about45 C., emulsifier(s) being present in either or both phases orseparately mixed with the two phases, the ratio of the flow rate of theoil phase to the flow rate of aqueous phase being within the range offrom about 5:1 to about 1:5, through a zone of high shear tointerdisperse and homogenize the phases and within a second thereaftercause them to congeal and form a semisolid emulsion.

